This post-doctoral fellowship training at the Yale School of Public Health is designed for Dr. Leyao Wang to broaden her knowledge and skills in the field of genetic epidemiology and to prepare her as an independent investigator. This will be accomplished through a number of academic activities such as internal and external courses, regular seminars, teaching opportunities and conferences, and a research project. One of the most significant risk factors associated with asthma onset and subsequent exacerbations is respiratory viral infections (RVIs), particularly with Human Rhinovirus (HRV) and Respiratory Syncytial Virus (RSV). RVIs are universal but the host response to it varies greatly and only a subset of individuals develops severe symptoms and asthma, termed virus-induced asthma. Some of the genetic variants associated with virus-induced asthma susceptibility have been identified through candidate gene association analysis, which has a limited research scope. To improve our knowledge on the underlying genetic variants contributing to virus-induced asthma vulnerability, a family-based whole-exome sequencing analysis will be conducted to uncover virus-induced asthma associated rare genetic variants within protein coding regions. Phenotype and genotype data for this study is from the ongoing parent R01 study entitled Family-specific genetic variants contributing to asthma susceptibility. Thirty eligible families will be selected from the 288 families segregating asthma among offspring in the parent study. These eligible families will have at least 2 asthmatic children with severe history of RVIs and at least 1 non-asthmatic child without severe history of RVIs. An association analysis will be performed on whole-exome sequencing data to search for significant rare variants associated with virus- induced asthma susceptibility. Significant genes harboring multiple rare variants will be identified. Biological validations will then be performed on genome-wide suggestive genes in in-vitro systems with RSV or HRV infection. Genetic variants in verified genes will be examined further to determine causal variants. This study aims to identify genetic components associated with virus-induced asthma in the hope of better elucidating the biological mechanisms through which virus infection modifies the risk for asthma. Dr. Leyao Wang will be exposed to this multidisciplinary project consisting of a multitude of approaches including epidemiologic data, biostatistics, bioinformatics and viral immunology, which is essential to her independent career development.